The use of DNA for immunizations represents a new approach to raising immune responses. This project addresses studies (i) the role of professional antigen presenting cells in the initiation of DNA-raised responses, (ii) parameters that determine whether a DNA-raised response will be biased towards Th1 or Th2 T-cell help, (iii) the type of cytolytic T-cells (CTL) raised by Th1 and Th2 DNA immunizations, (i.v.) the ability to use DNA to immunize neonatal mice. Studies on antibody and antibody-mediated protection will use DNAs expressing normal (membrane-bound) and secreted forms of the influenza H1 hemagglutinin glycoprotein and the A/PR/8/34 (H1N1) murine influenza virus model. Studies on CTL and CTL-mediated protection will use DNA expressing the influenza nucleoprotein (NP). Antigen presenting cells will be examined in draining lympoid tissue using DNA-expressing green flourescent protein and in vitro restimulation of H1-specific Th cell lines. Co-transfected lymphoki nes, lymphokine knock out mice, and lymphokine neutralizing antibodies will be used to analyze the dependence on lymphokines of the Th-biases of DNA raised responses. Studies on CTL will test for differences in frequency and function of CD8+ cells raised by Th1- and Th2-biased DNA immunizations. Studies on neonatal DNA immunization will be done in the presence and absence of maternal antibody. FUNDING NIH / NIAID $192,178 1/01/98 - 6/30/02 PUBLICATIONS Pertmer, T. and Robinson, H.L. Studies on antibody responses following neonatal immunization with influenza hemagglutinin DNA or protein. Virol. (In press). P51RR00165-38 1/1/1998 - 12/31/1998 Yerkes Regional Primate Research Center